Hypercalcemia: Causes, Complications, and Emergency Management

Hypercalcemia (serum calcium >10.5 mg/dL or >2.6 mmol/L ionized) is a common, potentially life-threatening metabolic emergency.

Etiology (Mnemonic: "CHIMPANZEES")

• Cancer (PTHrP, bony mets) — #1 inpatient cause.
• Hyperparathyroidism (primary) — #1 outpatient cause.
• Iatrogenic (thiazides, lithium, vit D/A toxicity, calcium supplements).
• Milk-alkali syndrome (CaCO₃ + alkali).
• PTHrP (humoral hypercalcemia of malignancy).
• Adrenal insufficiency.
• Neoplasms (hematologic: myeloma, lymphoma).
• Z (sarcoidosis, granulomatous — ↑1,25-vit D).
• Endocrine (thyrotoxicosis, pheochromocytoma).
• Extended immobilization.
• S (spurious: hemoconcentration, albumin elevation — correct for albumin).

Organ-System Complications

• Renal: Nephrolithiasis, nephrocalcinosis, diabetes insipidus (polyuria), AKI (vasoconstriction).
• Neurologic: Confusion, lethargy, coma, seizures.
• Cardiac: Shortened QT → arrhythmia risk; digitalis toxicity potentiation.
• GI: Nausea, vomiting, constipation, pancreatitis, peptic ulcer.
• Musculoskeletal: Bone pain, fractures (hyperparathyroidism).

Emergency Treatment (Calcium >14 mg/dL or symptomatic)

1. Aggressive IV hydration (NS 200–300 mL/hr) → target urine output 100–150 mL/hr.
2. Loop diuretic (furosemide) *after* volume repletion — enhances calciuresis.
3. Bisphosphonates: Zoledronic acid 4 mg IV (onset 24–48h, nadir 2–4d) or pamidronate. Denosumab 120 mg SC (renal-safe).
4. Calcitonin 4 IU/kg q12h (rapid but mild, tachyphylaxis).
5. Glucocorticoids (if vit D-mediated: lymphoma, sarcoid).
6. Dialysis (if renal failure, severe refractory).

Definitive Therapy

Treat underlying cause: parathyroidectomy (PHPT), oncology-directed therapy (malignancy), stop offending drugs.